PMID- 16648573 OWN - NLM STAT- MEDLINE DCOM- 20060919 LR - 20220309 IS - 1535-7163 (Print) IS - 1535-7163 (Linking) VI - 5 IP - 4 DP - 2006 Apr TI - Enhancement of tumor thermal therapy using gold nanoparticle-assisted tumor necrosis factor-alpha delivery. PG - 1014-20 AB - Tumor necrosis factor-alpha (TNF-alpha) is a potent cytokine with anticancer efficacy that can significantly enhance hyperthermic injury. However, TNF-alpha is systemically toxic, thereby creating a need for its selective tumor delivery. We used a newly developed nanoparticle delivery system consisting of 33-nm polyethylene glycol-coated colloidal gold nanoparticles (PT-cAu-TNF-alpha) with incorporated TNF-alpha payload (several hundred TNF-alpha molecules per nanoparticle) to maximize tumor damage and minimize systemic exposure to TNF-alpha. SCK mammary carcinomas grown in A/J mice were treated with 125 or 250 microg/kg PT-cAu-TNF-alpha alone or followed by local heating at 42.5 degrees C using a water bath for 60 minutes, 4 hours after nanoparticle injection. Increases in tumor growth delay were observed for both PT-cAu-TNF-alpha alone and heat alone, although the most dramatic effect was found in the combination treatment. Tumor blood flow was significantly suppressed 4 hours after an i.v. injection of free TNF-alpha or PT-cAu-TNF-alpha. Tumor perfusion, imaged by contrast enhanced ultrasonography, on days 1 and 5 after treatment revealed perfusion defects after the injection of PT-cAu-TNF-alpha alone and, in many regions, complete flow inhibition in tumors treated with combination treatment. The combination treatment of SCK tumors in vivo reduced the in vivo/in vitro tumor cell survival to 0.05% immediately following heating and to 0.005% at 18 hours after heating, suggesting vascular damage-mediated tumor cell killing. Thermally induced tumor growth delay was enhanced by pretreatment with TNF-alpha-coated gold nanoparticles when given i.v. at the proper dosage and timing. FAU - Visaria, Rachana K AU - Visaria RK AD - Department of Mechanical Engineering, University of Minnesota Medical School, Minneapolis, MN 55455, USA. FAU - Griffin, Robert J AU - Griffin RJ FAU - Williams, Brent W AU - Williams BW FAU - Ebbini, Emad S AU - Ebbini ES FAU - Paciotti, Giulio F AU - Paciotti GF FAU - Song, Chang W AU - Song CW FAU - Bischof, John C AU - Bischof JC LA - eng GR - CA44114/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PL - United States TA - Mol Cancer Ther JT - Molecular cancer therapeutics JID - 101132535 RN - 0 (Tumor Necrosis Factor-alpha) RN - 7440-57-5 (Gold) RN - MLT4718TJW (Rubidium) SB - IM MH - Animals MH - Biological Transport MH - Cell Survival/drug effects/physiology MH - *Gold MH - Hyperthermia, Induced MH - Mammary Neoplasms, Experimental/pathology/*therapy MH - Mice MH - Nanostructures MH - Rubidium/pharmacokinetics MH - Tumor Necrosis Factor-alpha/*pharmacokinetics/*therapeutic use EDAT- 2006/05/02 09:00 MHDA- 2006/09/20 09:00 CRDT- 2006/05/02 09:00 PHST- 2006/05/02 09:00 [pubmed] PHST- 2006/09/20 09:00 [medline] PHST- 2006/05/02 09:00 [entrez] AID - 5/4/1014 [pii] AID - 10.1158/1535-7163.MCT-05-0381 [doi] PST - ppublish SO - Mol Cancer Ther. 2006 Apr;5(4):1014-20. doi: 10.1158/1535-7163.MCT-05-0381.